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Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids' oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death. [ABSTRACT FROM AUTHOR]

Introduction: NF-κB plays a pivotal role in the progression of cancers, including myosarcomas such as fibrosarcoma. Plants possess considerable potential for the provision of chemotherapeutic effects against cancer. The present study assessed, among others, the cytotoxicity, migration capacity and DNA damage induced by several natural compounds (berberine, curcumin, biochanin A, cucurbitacin E (CurE) and phenethyl caffeic acid (CAPE)) in cancer cells (WEHI-164) and normal muscle cells (L6)., Methods: IC50 parameter was determined for all substances after 24-hour incubation. Molecular docking studies were performed to assess compound binding to cytoskeletal proteins. Neutral comet assay and immunocytochemical analysis were used to assess the intensity of apoptosis, and transmission electron microscopy was employed to validate these results at the ultrastructural level., Results and Discussion: The results showed that the tested compounds had a significantly increased cytotoxic effect on cancer cells compared to normal cells. Furthermore, molecular docking studies indicated that CAPE, biochanin A, and CurE could inhibit actin polymerization, suggesting their potential role in disrupting the cytoskeleton of cancer cells. Increased expression of caspase-3 and PARP-1 in WEHI-164 cells after treatment indicated the induction of apoptosis. Transmission electron microscopy confirmed the presence of cellular stress and vacuolation in cells treated with these compounds, with more pronounced effects observed in cancer cells compared to normal cells. The results indicate that natural NF-κB inhibitors may be capable of selectively targeting cancer cells, reducing their viability and inducing apoptosis while sparing normal cells. This selectivity is of great importance for the development of safer anticancer therapies. The results of this research support the hypothesis that these natural compounds may be effective anticancer agents, particularly in the treatment of fibrosarcoma. Further, in vivo studies and clinical trials are required to gain a full understanding of their mechanisms of action and potential synergies with existing chemotherapeutic agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Radzka, Gizak, Drąg-Zalesińska, Haczkiewicz-Leśniak, Kulus, Szewczyk, Szlasa, Podhorska-Okołów and Kulbacka.)

Background: Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3)., Objectives: The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA., Material and Methods: We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line., Results: After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells., Conclusions: Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.